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Journal of Virology, April 2004, p. 3753-3762, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3753-3762.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Low pH Is Required for Avian Sarcoma and Leukosis Virus Env-Induced Hemifusion and Fusion Pore Formation but Not for Pore Growth

G. B. Melikyan,1,{dagger} R. J. O. Barnard,2,{dagger},{ddagger} R. M. Markosyan,1 J. A. T. Young,2,{ddagger} and F. S. Cohen1*

Department of Molecular Biophysics and Physiology, Rush Medical College, Chicago, Illinois 60612,1 Department of Oncology, University of Wisconsin-Madison, Madison, Wisconsin 537062

Received 7 August 2003/ Accepted 4 December 2003

Binding of avian sarcoma and leukosis virus (ASLV) to its cognate receptor on the cell surface causes conformational changes in its envelope protein (Env). It is currently debated whether low pH is required for ASLV infection. To elucidate the role of low pH, we studied the association between ASLV subgroup B (ASLV-B) and liposomes and fusion between effector cells expressing Env from ASLV-A and ASLV-B and target cells expressing cognate receptors. Neither EnvA nor EnvB promoted cell-cell fusion at neutral pH, but lowering the pH resulted in quick and extensive fusion. As expected for a low-pH-triggered reaction, fusion was a steep function of pH. Steps that required low pH were identified. Binding a soluble form of the receptor caused ASLV-B to hydrophobically associate with liposome membranes at neutral pH, indicating that low pH is not required for insertion of Env's fusion peptides into membranes. But both cell-cell hemifusion and fusion pore formation were pH dependent. It is proposed that fusion peptide insertion stabilizes the conformation of ASLV Env into a form that can be acted upon by low pH. At this point, but not before, low pH can induce fusion and is in fact required for fusion to occur. However, low pH is no longer necessary after formation of the initial fusion pore: pore enlargement does not require low pH.

* Corresponding author. Mailing address: Department of Molecular Biophysics and Physiology, Rush Medical College, 1653 W. Congress Pkwy., Chicago, IL 60612. Phone: (312) 942-6753. Fax: (312) 942-8711. E-mail: fcohen{at}rush.edu.

{dagger} G.B.M. and R.J.O.B. contributed equally.

{ddagger} Present address: The Infectious Disease Laboratory, The Salk Institute, La Jolla, San Diego, CA 92037.

Journal of Virology, April 2004, p. 3753-3762, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3753-3762.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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